Role of Deleterious Rare Alleles for Acute-Onset Diffuse Interstitial Lung Disease in Collagen Diseases.

ABSTRACT: Objective:Acute-onset diffuse interstitial lung disease (AoDILD) includes acute exacerbation of interstitial lung disease (ILD), drug-induced ILD, and Pneumocystis pneumonia in collagen diseases patients. As AoDILD causes a poor prognosis in collagen disease patients, the pathogenesis of AoDILD should be investigated. Exome sequencing studies revealed that rare variants were detected to be causative in some diseases. Recently reported upregulated genes in acute exacerbation of idiopathic pulmonary fibrosis could provide candidate genes for restricted exome analysis of AoDILD in collagen disease. Here, we investigated rare variants in the coding and boundary regions of these candidate genes in AoDILD. Methods:Deleterious rare variants in the coding and boundary regions of the candidate genes were analyzed by exome sequencing and the deleterious rare allele frequencies in AoDILD were compared with those of controls. Results:A significant association was detected for deleterious rare alleles in NPL (P?=?.0044, P c?=?.0399, odds ratio [OR]?=?10.05, 95% confidence interval [CI]?=?3.01-33.55). A deleterious rare allele frequency in the 9 candidate genes (P?=?.0011, OR?=?7.17, 95% CI?=?2.80-18.33) was also increased in AoDILD in multigene panel analysis. The Krebs von den Lungen-6 (KL-6) levels in AoDILD patients with deleterious rare alleles were tended to be lower than those without (P?=?.0168, P c?=?.1509). Conclusions:The deleterious rare alleles in NPL were associated with AoDILD. In addition, the deleterious rare allele frequency in the 9 candidate genes was also increased in AoDILD. The deleterious rare alleles might contribute to the pathogenesis of AoDILD.

SUBMITTER: Furukawa H 

PROVIDER: S-EPMC6668171 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature